SEMINAR

Competing pathway of solubility-limited formation of protein aggregates

Abstract
Protein aggregates such as amyloids and amorphous aggregates cause various diseases including Alzheimer’s disease. These aggregates are two types of protein precipitations and form above their solubilities (1). Amyloid fibrils, similar to crystals, have highly ordered structure that form through nucleation and elongation. On the other hand, amorphous aggregates have less ordered structure and form without a lag phase. Their formations were comprehensively explained by a competing mechanism in which amyloid fibrillation and amorphous aggregation occurred competitively through a supersaturation-limited and supersaturation-unlimited pathways, respectively (2). This produced a complicated kinetics under the conditions where both amyloid fibrils and amorphous aggregates are accessible; thermodynamically more stable amyloid fibrils form slowly through a transient accumulation of kinetically more accessible amorphous aggregates. We linked the kinetics of protein aggregation and a conformational phase diagram, in which supersaturation played important roles.

References

[1] Y. Yoshimura, et al (2012) Distinguishing crystal-like amyloid fibrils and glass-like amorphous aggregates from their kinetics of formation. Proc. Natl. Acad. Sci. USA 109, 14446-14451.

[2] M. Adachi, M. So, et al. (2015) Supersaturation-limited and unlimited phase transitions compete to produce the pathway complexity in amyloid fibrillation. J. Biol. Chem. 290, 18134-18145.

BIOGRAPHY

2015-present: Assistant Professor, Institute for Protein Research, Osaka University, Japan
2013-2015: JSPS fellow, Institute for Protein Research, Osaka University, Japan
2014: PhD, Graduate School of Science, Osaka University, Japan

Research Fields and Interests:
Mechanisms of amyloid fibrillation and structure and physical properties of amyloid fibrils. Clarifying the mechanism of protein aggregation is important for treating many diseases such as Alzheimer’s and Parkinson’s diseases. We study the mechanism of amyloid fibrillation and amorphous aggregation using various spectroscopies including CD, fluorescence, FTIR, and solution NMR. We also investigate the structure of amyloid fibrils using solid state NMR.

Selected Publications:

So, M., Ishii, A., Hata, Y., Yagi, H., Naiki, H., and Goto, Y. (2015) Supersaturation-limited and unlimited phase spaces compete to produce maximal amyloid fibrillation near the critical micelle concentration of sodium dodecyl sulfate. Langmuir, revision submitted.

Adachi, M., So, M., Sakurai, K., Kardos, J., and Goto Y. (2015) Supersaturation-limited and unlimited phase transitions compete to produce the pathway complexity in amyloid fibrillation. J. Biol. Chem. 290, 18134-18145.

Umemoto, A., Yagi, H., M., So, and Goto Y. (2014) High-throughput analysis of ultrasonication-forced amyloid fibrillation reveals the mechanism underlying the Large Fluctuation in the Lag Time. J. Biol. Chem. 289, 27290-27299.

Yoshimura, Y., So, M., Yagi, H., and Goto, Y. (2013) Ultrasonication: an efficient agitation for accelerating the supersaturation-limited amyloid fibrillation of proteins. Jpn. J. Appl. Phys. 52, 07HA01.

Yoshimura, Y., Lin, Y., Yagi, H., Lee, Y.-H., Kitayama, H., Sakurai, K., So, M., Ogi, H., Naiki, H., and Goto, Y. (2012) Distinguishing crystal-like amyloid fibrils and glass-like amorphous aggregates from their kinetics of formation. Proc. Natl. Acad. Sci. USA 109, 14446-14451.